Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results: Incidence and Characterization in a Large, Contemporary United States Cohort.
Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results: Incidence and Characterization in a Large, Contemporary United States Cohort.
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DOI：
10.1097/pas.0000000000001685
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发表时间：
2021-07-01
期刊：
影响因子：
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通讯作者：
Lewis JS Jr
中科院分区：
文献类型：
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作者：
Shinn JR;Davis SJ;Lang-Kuhs KA;Rohde S;Wang X;Liu P;Dupont WD;Plummer D Jr;Thorstad WL;Chernock RD;Mehrad M;Lewis JS Jr
早期研究估计，5% 至 10% 的口咽鳞状细胞癌过度表达 p16，但与转录活性高危人乳头瘤病毒 (HPV) 无关。 HPV 检测不一致的患者可能会经历与传统预期不同的临床结果。为了记录 p16 和 HPV mRNA 阳性率，表征检测不一致的患者，并确定 p16 IHC 后可能需要选择性使用 HPV 特异性检测的特征，对口咽鳞状细胞癌患者进行了 p16 IHC 和逆转录酶聚合酶链反应 HPV mRNA 检测的多机构回顾性审查。在 467 名患者中，大多数患有 T1 或 T2 肿瘤（71%），82% 为 p16 阳性，84% 为 HPV mRNA 阳性。总体而言，大多数肿瘤是非角化性的（378%、81%），这与 p16 和 HPV 阳性（分别为 93% 和 95%）密切相关。总体而言，81% 的患者为双阳性，14% 为双阴性，4.9% 为不一致（3.4% p16 阴性/HPV mRNA 阳性，1.5% p16 阳性/HPV mRNA 阴性）。这些不一致患者组的生存率直接落在两个一致组之间，尽管在无病生存率和总生存率的多变量分析中，没有发现不一致患者具有统计学上显着不同的结果。当 p16 结果和形态不匹配或 p16 结果模棱两可时，通过应用 HPV mRNA 检测对患者进行重新分类，与单独使用 p16 或 HPV mRNA 检测相比，可略微改善预后。测试不一致的患者与测试一致的患者相比，表现出生存差异的临界显着趋势。独立评估时，p16阴性但HPV mRNA阳性的患者预后更接近双阳性患者，而p16阳性但HPV mRNA阴性的患者预后更接近双阴性患者。我们建议采用一种算法，对 p16 状态与肿瘤形态不一致的患者进行确认性 HPV mRNA 检测。这捕获了大多数不一致的患者，并改善了（尽管是适度的）预测。
Early studies estimate that 5% to 10% of oropharyngeal squamous cell carcinomas overexpress p16 but are unassociated with transcriptionally-active high-risk human papillomavirus (HPV). Patients with discordant HPV testing may experience clinical outcomes that differ from traditional expectations. To document the rate of p16 and HPV mRNA positivity, characterize patients with discordant testing, and identify features that may warrant selective use of HPV-specific testing after p16 IHC, a multi-institutional, retrospective review of oropharyngeal squamous cell carcinoma patients with p16 IHC and HPV mRNA testing by reverse transcriptase polymerase chain reaction was performed. Of the 467 patients, most had T1 or T2 tumors (71%), 82% were p16 positive, and 84% were HPV mRNA positive. Overall, most tumors were nonkeratinizing (378, 81%), which was strongly associated with p16 and HPV positivity (93% and 95%, respectively). Overall, 81% of patients were double positive, 14% double negative, and 4.9% discordant (3.4% p16 negative/HPV mRNA positive and 1.5% p16 positive/HPV mRNA negative). The survival rates of these discordant patient groups fell squarely between the 2 concordant groups, although in multivariate analysis for both disease-free survival and overall survival, discordant patients were not found to have statistically significantly different outcomes. Reclassifying patients by applying HPV mRNA testing when p16 results and morphology do not match, or when p16 results are equivocal, improved prognostication slightly over p16 or HPV mRNA testing alone. Patients with discordant testing demonstrate a borderline significant trend toward survival differences from those with concordant tests. When evaluated independently, patients who were p16 negative but HPV mRNA positive had a prognosis somewhat closer to double-positive patients, while those who were p16 positive, but HPV mRNA negative had a prognosis closer to that of double-negative patients. We suggest an algorithm whereby confirmatory HPV mRNA testing is performed in patients where p16 status is not consistent with tumor morphology. This captures a majority of discordant patients and improves, albeit modestly, the prognostication.